Clinical and preclinical observations suggest that methamphetamine may cause long-lasting injury to the brain. However, there are no studies that assessed the extent of brain injury and monitored the success of therapy for methamphetamine abuse. Our aims are: 1) to assess fro persistent neuronal or glial injury with 1H MRS, and for neuropsychological abnormalities, in recently abstinent methamphetamine- dependent subjects; 2) to determine whether effective cognitive behavioral therapy for methamphetamine-dependence is associated with improvement of neurochemical abnormalities (as detected by 1H MRS) and cognitive function; 3) to determine if changes in neurochemical concentrations correlate with changes in cognitive function, both before and after treatment. Preliminary studies from our laboratory demonstrate that chronic methamphetamine abuse is associated with clear evidence for brain injury. Cerebral metabolite concentrations measured by in vivo proton magnetic resonance spectroscopy (1H MRS), including the glial marker, myoinositol, and the neuronal marker, N-acetyl aspartate are reduced, along with decreased performance on neuropsychological tests, in abstinent methamphetamine abusers. Furthermore, subjects with longer periods of abstinence and treatment showed improved cerebral metabolite concentrations to approach normal values. Based on our preliminary data, we hypothesize: (1) After 4-6 weeks of abstinence, 1H MRS will show persistent brain injury in the basal ganglia and the frontal lobes of methamphetamine abusers compared to healthy control subjects matched by age, gender, and socioeconomic status. (2) After five months of successful treatment, and even more so after 10 months, some of the initially abnormal metabolite concentrations will improve in subjects with continued abstinence. (3) After 10 months of successful treatment, changes in performance on specific neuropsychological tests will depend on changes in metabolite concentrations. (4) In subjects who relapse, the severity of the initial metabolite abnormalities will predict the length of time to relapse. Localized 1H MRS, neurological, psychiatric and neuropsychological evaluations (including CalCAP, a set of computerized reaction time tasks), will be performed repeatedly in 72 subjects with a history of methamphetamine dependence at 4-6 weeks, at 5 and at 10 months after initiation of their treatment program. This comprehensive approach will allow us to determine the relationship between changes in cognitive function and metabolite changes in brain tissue associated with chronic methamphetamine abuse and treatment.